Abstract - Epicenter IV: Harvard Pilgrim-UCI Center for HAI Prevention (Core) We propose five core aims evaluating novel (T0-T1) strategies to detect and prevent healthcare- associated infections and the emergence of antibiotic resistance among healthcare-associated pathogens. These aims have high potential to lead to improvements in health outcomes, take advantage of prior work in these domains, and strengthen our infrastructure to respond to new topics CDC may ask the Epicenters to address. Projects covered include the following: 1) Detecting hospital outbreaks using statistical software to evaluate whether the benefit observed from universal decolonization ICUs was mediated by prevention of clusters. This T1 work will involve a secondary analysis of the completed REDUCE MRSA Trial. Two projects deal with prevention of antibiotic resistance: 2) Evaluating the impact of substituting nasal iodophor for mupirocin when paired with chlorhexidine for ICU universal decolonization. The Mupirocin-Iodophor Swapout trial will be a 120 hospital T2 cluster-randomized trial assessing the non-inferiority of iodophor on S. aureus clinical cultures and all-pathogen bloodstream infections. It will assess whether nasal antiseptics can mitigate the emergence of resistance seen with mupirocin use. 3) Re-engineering the hospital antibiogram to provide treating physicians with the likelihood that patient's pneumonia or a urinary tract infection is due to a multi-drug resistant pathogen. This T1 study will create a novel antibiogram that could aid empiric antibiotic selection and prevent extended spectrum antibiotics from being unnecessarily prescribed. Two final projects involve the development or improvement of national metrics for serious inpatient diseases. 4) Assessing the impact of nationally reported compliance with sepsis bundles on patient outcomes. This T0 work will critically evaluate metrics to prevent adverse outcomes associated with sepsis. 5) Developing an objective surveillance definition for non-ventilator hospital-acquired pneumonia. This T0 work will leverage our experience re-defining national metrics for ventilator-associated pneumonia and will similarly align explicit, computable definitions with clinical outcomes.